Cardio Pharm Flashcards

Question

Heparin

Answer 1

Antithrombin III activator - highly sulfated mucopolysaccharide , highly negative - not absorbed from GI tract, not effective orally. -allosteric binding exposes a reactive site accessible to Factor Xa and thrombin -heparin is then released and still cna form more antithrombin-protease complexes. -Unfractionated heparin has higher specificity as it can make a complex with both Antithrombin and thrombin (as opposed to LMW heparin) _________________________________ Reversal of heparin action: -discontinue usage of the drug -protamine sulfate is an effective antidote (fish sperm highly positive), only effective against LMWH and itself has anticoag activity. ________________________________ Toxicity: 1. major bleeding 2. Osteoporosis (higher with UFH) 3. Heparin resistance - elevated factor VIII or other proteins, antithrombin deficiency, increased clearance 4. Heparin induced thrombocytopenia- heparin acts as a haptin, antibodies are binding and activating platelets, platelet count will drop in plasma and you clot because platelets are releasing particles that activate thrombin.

Answer 2

``` indirect thrombin inhibitor (relative to heparin)... ________________________ -less inhibition of thrombin -efficiently inhibit factor Xa activity -longer half life (4.5 hrs) less frequent dosing ``` Uses: - prevention of DVT in postsurgery - treat acute venous thromboembolic disease and acute coronary syndromes * more predictable bioavailability

Answer 3

indirect thrombin inhibitor ``` Synthetic analog of the pentasaccharide binding sequence of heparin *target is only Factor Xa _________________ • Pharmacokinetics – long half-life (17-21 h) – 100% bioavailable after a single, daily, subcutaneous dose – Renal clearance, should not be given to patients with renal impairment • Low incidence of HIT *more predictable bioavailability ```

Answer 4

65 amino acid protein found in medicinal leech (Hirudo medicinalis). • Most potent known inhibitor of thrombin. • Action is independent of antithrombin III • Can reach and inactivate fibrin-bound thrombin in thrombi • Does not cause thrombocytopenia • Approved- prevention of deep vein thrombosis post elective hip replacement •t1/2 = 2 hours • Renal clearance -binds to exosite 1 of thrombin and catalytic (active) site

Answer 5

(Direct thrombin inhibitor) • Synthetic peptide congener of hirudin • Short half life (~25 min) • Clearance: renal & metabolic • FDA approved for use in coronary angioplasty, also in patients with HIT -binds to exosite 1 of thrombin and catalytic (active) site

Answer 6

-direct thrombin inhibitor (only binds to active site of thrombin) • Administered IV • FDA approved for use as an anticoagulant in patients with heparin-induced thrombocytopenia (HIT). • Pharmacokinetics • Half-life 40-50 minutes. • metabolized by the liver and eliminated in the bile • Monitored by aPTT, also prolongs PT (note when use with warfarin). • aPTT returns to normal two hours after discontinuing treatment. _______________________________ [Adverse effects] • hemorrhage (2%) • allergic reactions (10%)

Answer 7

99% bound to albumin (drug interactions) -inhibits biosynthesis of vitamin K dependent zymogens ``` [Procoag] Prothrombin Factor VII Factor IX Factor X ``` [Anticoag] Protein C Protein S MOA: blocks vitamin K reductase VKORC1 activity, reduced vitamin K is needed by glutamyl carboxylase to make functional zymogens by carboxylating and making GLA residues. -Early on with usage, protein C level goes down early and you are in a procoagulant state. _________________________ warfarin has a low therapeutic index 1.-bleeding 2. Birth defects and abortion -Skeletal and CNS abnormalities (hypoplastic nose, flat face, altered calcification) -Contraindicated during pregnancy (heparin may be used) 3. Skin necrosis - Microvascular thrombosis - May occur in patients with heterozygous protein C or S deficiency if a high initial dose is used or heparin overlap is inadequate

Answer 8

direct thrombin inhibitor Non-inferiority/superiority to warfarin Less intracranial bleeding than warfarin (at least 50% lower) **GI bleeding higher for dabigatran, rivaroxaban and edoxaban Other sites, similar overall bleeding Similar uses to warfarin but contraindicated in patients with mechanical heart valves **Claimed that routine coagulation monitoring not necessary due to predictable response (benefit) Antidote for Dabigatran: Idarucizumab, humanized mAb

Answer 9

Non-inferiority/superiority to warfarin Less intracranial bleeding than warfarin (at least 50% lower) **GI bleeding higher for dabigatran, rivaroxaban and edoxaban Other sites, similar overall bleeding Similar uses to warfarin but contraindicated in patients with mechanical heart valves **Claimed that routine coagulation monitoring not necessary due to predictable response (benefit)

Answer 10

direct factor Xa inhibitor Non-inferiority/superiority to warfarin Less intracranial bleeding than warfarin (at least 50% lower) **GI bleeding higher for dabigatran, rivaroxaban and edoxaban Other sites, similar overall bleeding Similar uses to warfarin but contraindicated in patients with mechanical heart valves **Claimed that routine coagulation monitoring not necessary due to predictable response (benefit)

Answer 11

Non-inferiority/superiority to warfarin Less intracranial bleeding than warfarin (at least 50% lower) **GI bleeding higher for dabigatran, rivaroxaban and edoxaban Other sites, similar overall bleeding Similar uses to warfarin but contraindicated in patients with mechanical heart valves **Claimed that routine coagulation monitoring not necessary due to predictable response (benefit)

Answer 12

recombinant tPA Physiologically t-PA activates plasminogen that is bound to fibrin of thrombus, • plasmin activation at the site of clot is several hundred times higher than unbound plasminogen. • Clinical concentrations are much higher than physiological concentrations • Non-specific plasmin activation • Half-life ~ 5 min in plasma. Typically IV bolus then infusion ____________________________ • Approved uses - Acute MI - Acute ischemic stroke - Pulmonary embolism - Central venous catheter occlusion [Absolute Contraindications] • Prior intracranial hemorrhage • Known structural cerebral vascular lesion • Known malignant intracranial neoplasm • Ischemic stroke within 3 months • Suspected aortic dissection • Active bleeding or bleeding diathesis (excluding menses) • Significant closed-head trauma or facial trauma within 3 months [Relative Contraindications] • Uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg) • Traumatic or prolonged CPR or major surgery within 3 weeks • Recent (within 2-4 weeks) internal bleeding • Noncompressible vascular punctures • Pregnancy • Active peptic ulcer • Current use of warfarin and INR >1.7

Answer 13

Aspirin inhibits thromboxane A2 (TxA2) synthesis by irreversibly acetylating cyclooxygenase-1 (COX-1). Reduced TxA2 release attenuates platelet activation and recruitment to the site of vascular injury. Platelets have no nucleus & cannot regenerate COX. Effect lasts the life of the platelet (7-10 days). •Endothelial cells can regenerate COX to produce PGI2, restoring antithrombotic effect. •Endothelial cyclooxygenase requires higher doses of aspirin for inhibition. Low dose (70-325 mg/day) can selectively inhibit platelet COX, sparing endothelial COX and thus sustaining antithrombotic effect. •Primary prophylaxis of myocardial infarction; secondary prevention vascular events following heart disease •Adverse effects: BLEEDING (hemorrhagic stroke, GI bleeding),  risk of peptic ulcer disease

Answer 14

Irreversibly inhibits the binding of ADP to its receptor on platelets, inhibits platelet aggregation ((blocks P2Y12, a key ADP receptor on the platelet surface; cangrelor and ticagrelor are reversible inhibitors of P2Y12.) [Indications and; adverse effects] • Dual antiplatelet therapy (e.g., coronary artery stenting) – ADP inhibitor + aspirin • Triple therapy (e.g., coronary artery stenting plus atrial fibrillation) – Oral anticoagulant + ADP inhibitor + aspirin • BLEEDING

Answer 15

Irreversibly inhibits the binding of ADP to its receptor on platelets, inhibits platelet aggregation ((blocks P2Y12, a key ADP receptor on the platelet surface; cangrelor and ticagrelor are reversible inhibitors of P2Y12.) Indications and; adverse effects • Dual antiplatelet therapy (e.g., coronary artery stenting) – ADP inhibitor + aspirin • Triple therapy (e.g., coronary artery stenting plus atrial fibrillation) – Oral anticoagulant + ADP inhibitor + aspirin • BLEEDING thrombotic thrombocytopenia purpurae

Answer 16

GPIIb/IIIa is a platelet membrane receptor which binds to the fibronogen and vitronectin and also to fibronectin and von Willebrand Factor, facilitates formation of platelet plug. monoclonal antibody directed against GPIIb/IIIa complex • approved for use in coronary angioplasty and in acute coronary syndrome.

Answer 17

Reversibly inhibits the binding of ADP to its receptor on platelets, inhibits platelet aggregation (blocks P2Y12, a key ADP receptor on the platelet surface; ticagrelor is the only reversible inhibitors of P2Y12.)\ ***-ticlopidine - causes neutropenia -metabolized by P450 enzymes so poor metabolizers are more at risk Indications AND; adverse effects • Dual antiplatelet therapy (e.g., coronary artery stenting) – ADP inhibitor + aspirin • Triple therapy (e.g., coronary artery stenting plus atrial fibrillation) – Oral anticoagulant + ADP inhibitor + aspirin • BLEEDING -thrombotic thrombocytopenia purpurae

Answer 18

GPIIb/IIIa is a platelet membrane receptor which binds to the fibronogen and vitronectin and also to fibronectin and von Willebrand Factor, facilitates formation of platelet plug. Designed as a non-peptide analog of amino acid sequence Arg-Gly-Asp (RGD), which is the main recognition sequence of GPIIb/IIIa receptors. • Occupies receptor, inhibits binding.

Answer 19

GPIIb/IIIa is a platelet membrane receptor which binds to the fibronogen and vitronectin and also to fibronectin and von Willebrand Factor, facilitates formation of platelet plug. cyclic peptide derivative based on peptides present in pit viper venom. • Analog of the sequence which mediates the binding of fibrinogen to the receptor. • Occupies receptor, inhibits binding.

Answer 20

1. increases renal blood flow 2. block sodium reabsorption 3. blocks the tuberoglomerular feedback 4. blocks calcium reabsoprtion Sulfonamide loop diuretics. Block cotransporter NKCC2 cotransport system (Na+/K+/2Cl−) of thick ascending limb of loop of Henle. Abolish hypertonicity of medulla, preventing concentration of urine. Stimulate PGE release (vasodilatory effect on afferent arteriole) increasing filtration; inhibited by NSAIDs. increase Ca2+ and magneisum excretion. Loops Lose Ca2+. NKCC2 brings in one sodium, one potassium, 2 chloride. Potassium leaks back into the lumen creating a net potential that favors positively charged magnesium and calcium reabsorption. -Loop diuretics block tubuloglomerular feedback by inhibiting salt transport into the macula densa. • CLINICAL USE ACUTE Edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), ACUTE hypercalcemia. ``` [ADVERSE EFFECTS] Ototoxicity, Hypokalemia, Hypomagnesemia, Dehydration, Allergy (sulfa), metabolic Alkalosis: enhanced proximal sodium reabsorption > increased proton/sodium exchange Nephritis (interstitial), Gout. -increased proximal uric acid reabsorption > gout ``` •  Monitoring of K+ levels is critical with diuretics. Low K+ can unveil ectopic pacemakers and cause arrythmias. *   Loop agents induce prostaglandin and NO generation from endothelial cells, which reduce venous return and pulmonary congestion. *   FA *Ethacrynic acid is indicated for patients allergic to sulfonamides, but can cause more ototoxicity than furosemide. *   Furosemide is the most widely used. All loop agents are orally available with a duration of action ranging from 4-8 hours (6 hours for furosemide). Potassium wasting: Diuretics that act upstream of the collecting tubule will increase Na+ delivery to this site and will enhance K+ secretion. This mechanism, combined with enhanced aldosterone secretion due to volume depletion, is the basis for most diuretic-induced K+ wasting and proton secretion.

Answer 21

Renin Blockers: Aliskiren is a nonpeptidic drug that inhibit the protease renin (IC nM). Aliskiren is orally available with a half-life of 20-45 h in plasma. Aliskiren was FDA approved for the treatment of hypertension in March 2007. Clinical Trials are underway to evaluate its efficacy for heart failure treatment. Similar side effects to ACE inhibitors.

Answer 22

Hydralazine plus isosorbide dinitrate (BiDil): - the isosorbide dinitrate is a nitric oxide donor which increases cGMP causing smooth muscle relaxation. Hydralazine works under unkown mechanisms but both vasodilates arterioles > veins; afterload reduction. USES: Severe hypertension (particularly acute), HEART FAILURE - especially for African Americans!! (with organic nitrate). Safe to use during pregnancy. Frequently coadministered with a β-blocker to prevent relex tachycardia. Compensatory tachycardia (contraindicated in angina/CAD), luid retention, headache, angina. ***Lupus-like syndrome (mentioned in first aid) Helpful but less effective than ACE inhibitors in all current survival studies. •  May be particularly effective in a subset of black patients, who have been reported to be less responsive to ACE inhibitors, when added to standard treatments. •  May be added to patients with persistent symptoms -if an ACE inhibitor isn't working, you can add it on

Answer 23

Dual inhibition of neprilysin (breaks down natruiretic peptide); sacubitril) and angiotensin receptors (valsartan) with LCZ696 reduces mortality and hospitalization for heart failure compared to ACE inhibitor. FDA approved July 2015. Shown to decrease mortality compared to ACE inhibitor enalapril. Side effects: hypotension, hyperkalemia (blocking angiotensin II) and renal failure.

Answer 24

Nitroprusside: Short acting; increase cGMP via direct release of NO. Can cause cyanide toxicity (releases cyanide) - metabolic acidosis, cardiac arrhythmias USE: hypertensive EMERGENCY - like pulmonary edema - decrease renal perfusion will increases renin so always requires combination with loop diuretics Dilates both arterial and venous vessels. Given by I.V. for acute H.F. Half-life is 2 min. Dilates arterial and venous vessels to increase C.O. -NO SpECIFICITY Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate (enzymaticlly reduced to RSNO which is reduced to NO by tissue enzymes which confers tissue specificity) ``` Topical Nitrates (e.g. nitroglycerin): Decreases pulmonary and systemic venous pressures and left ventricle filling pressure, but it has a variable effect on cardiac output. -specifically acts on VEINS unlike nitroprusside (increase venous capacitance, decrease LVEDV and LEDP, decrease myocardial oxygen demand, increases subendocardial perfusion from decreased pressure) ``` -Vasodilate by increasing NO in vascular smooth muscle > increase in cGMP and smooth muscle relaxation. Dilate veins >> arteries. Decrease preload. Uses: Angina, acute coronary syndrome, pulmonary edema, esophageal spasm (relaxes the muscle) Adverse effect: HEADACHE #1, flushing, postural hypotension, Reflex tachycardia (treat with β-blockers), hypotension, flushing, “Monday disease” in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend > tachycardia, dizziness, headache upon reexposure. Contraindicated in right ventricular infarction.

Answer 25

1. Cardiac glycosides (digitalis, digoxin, digitoxin, and ouabain) block the Na/K pump •  Increased [Na+]i oppose action of Na+-Ca2+ exchanger NCX, raising cytosolic [Ca2+] •  Increased cytosolic [Ca2+] increases Ca2+ levels in sarcoplasmic reticulum (SR). •  Action potential then release greater-than-normal Ca2+ to increase contraction. •  K+ antagonizes action of digitalis. Monitoring of K+ is essential due to side-effects. Too little potassium can also make digoxin work TOO well. So watch out for thiazides and loops. -low therapeutic index **Digoxin is used almost exclusively in therapy. T1/2 = 36-40 hrs •  Cardiac glycosides increase C.O., decrease heart size, decrease venous pressure, decrease E.D.V, produce diuresis (increase renal perfusion), and decrease blood/ECF volume due to increased cardiac contractility from altered calcium dynamics. Also Observe: A. Decreased sympathetic output (direct and reflex) and increased vagal activity. In addition, there is a decrease in heart rate and increased vasodilation. B. Increased renal perfusion. C. Some inhibition of renal Na+/K+ ATPase promoting Na+ excretion and diuresis. D. Improved renal perfusion dynamics and reduced renin output. THERAPEUTICALLY: 1.  Digitalis enhances vagal tone and reduces sympathetic activity. 2. Slows conduction velocity and increases refractoriness in AV node •  Reduces rate of ventricular stimulation in patients with atrial fibrillation or flutter •  Can convert some supraventricular reentrant arrhythmias to normal rhythm. AT TOXIC LEVELS: •  AV block •  Further enhancement of vagal tone and extreme inhibition of the Na/K pump negatively affects cells in the atria and in ventricular Purkinje fibers and promotes many forms of arrhythmias. •  Increases sympathetic outflow, sensitizing the myocardium OTHER SIDE EFFECTS: nausea, vomiting, visual disturbances •  Digitalis-induced tachyarrhythmias treated with K+, if hypokalemia is present, lidocaine, or Digitalis antibody

Answer 26

β1 receptor activates adenylate cyclase to make cAMP. cAMP activates protein kinases, which promote intracellular calcium influx by phosphorylated slow L-type calcium channel. Increased calcium influx increases Ca2+ levels in the SR to increase contraction. * DOBUTAMINE: Useful for treatment of heart failure not accompanied by hypotension. •  A synthetic analog of dopamine that stimulates β1-β2, and α-receptors. Increases contractility through β1 effect, but does not increases peripheral resistance because β2- and αreceptor effects balance out. Does not stimulate dopaminergic receptors nor increase release of norepinephrine. •  Dobutamine is a racemic mixture with a half-life of ~ 2.5 min. •  (+) isomer: beta1> beta2 agonist, alpha1 antagonist •  (-) isomer: alpha1 agonist •  NOREPINEPHRINE: Acts at β1 and peripheral α-receptors. Useful for stimulating heart under conditions in which there is drop in blood pressure. Used for “warm” septic shock. * EPINEPHRINE: Acts at β1, β2 and peripheral α-receptors. Useful for increasing contraction and heart rate. Used for “cardiac arrest”. Contraindicated in patients receiving β-blocker therapy because of risk of α-mediated severe hypertension.

Answer 27

Phosphodiesterase inhibitors: (Milrinone and Enoximone): [FA} Selective PDE-3 inhibitor. In cardiomyocytes: increase cAMP accumulation > increase Ca2+ influx > increased inotropy and chronotropy. In vascular smooth muscle: increase cAMP accumulation > inhibition of MLCK activity > general vasodilation. CLINICAL USE Short-term use in acute decompensated HF. ADVERSE EFFECTS: Arrhythmias, hypotension. ____________________________ Selective for phosphodiesterase isozyme 3 (PDE3), found in cardiac and smooth muscle. •  In heart see increased cAMP and phosphorylation/activation of L-type calcium channels, raising Ca2+ and increasing myocardial contractility. •  In vascular smooth muscle see increased cAMP-mediated deactivation of myosin light chain kinase, causing vasodilation. •  Safe and effective for short-term (<24 hr) support of decompensated heart failure or for an exacerbation of chronic heart failure. Useful when other treatments are failing. Less prone to produce arrhythmias than adrenergics or digitalis. •  Toxicity: Milrinone causes fatal arrhythmias, bone marrow and liver toxicity. Long term use is not warranted. These are not 1st line, use beta agonists in acute settings

Answer 28

Block AT1 receptors •  Similar to ACE inhibitors, ARBs decrease afterload by lowering peripheral resistance and reduce preload by reducing aldosterone secretion. •  Long-term therapy with ARBs reduces the risk of death and other cardiovascular events in patients with heart failure; results are comparable to those obtained with ACE inhibitors. •  Similar side effects (e.g. hypotension) to ACE inhibitors except for cough and rarely angioedema …. Increased **fetal mortality. Ang II important for fetal differentiation -Worsen Renal Insufficiency - Disproportionate glomerular efferent arterial vasodilation. •  Does not affect bradykinin duration, or its production of prostaglandins or NO. More selective for inhibition of the effects of Ang. II because there are other enzymes other than ACE that can generate Ang. II. •  Large clinical trials suggest that the ARBs should only be used in patients who are intolerant of ACE inhibitors (usually because of cough) because ACE is still therapeutically more effective .

Answer 29

Prototype is procainamide, others are quinidine and disopyramide Increased AP duration, increased effective refractory period (ERP) in ventricular action potential, increased QT interval, some potassium channel blocking effects. USES: most effective for AFIB + ventricular arrhythmias FA/ Both atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT. WPW SYNDROME🎇 Slows upstroke of action potential and prolongs action potential duration. Bind to Na+ and K+ channels with intermediate kinetics and moderate affinity. - increases QRS duration, increase QT which can lead to Torsades. Procainamide is effective against most atrial and ventricular arrhythmias- broad spectrum -indicated for *VT with remote myocardial infarction Toxicity: 😑Procainamide reduces peripheral vascular resistance 😒Slowing of conduction and action potential prolongation increases risk of torsade de pointes, syncope and precipitation of new arrhythmias. ⭐️Procainamide can cause a syndrome resembling lupus erythematosus in 1/3 of patients receiving long-term therapy Quinidine can cause cinchonism - ringing of the ears Disopyramide can **cause atropine-like adverse effects: urinary retention, dry mouth, blurred vision, constipation, and worsening of preexisting glaucoma. 🌞Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide), thrombocytopenia, torsades de pointes due to increased QT interval. Procainamide is eliminated by hepatic metabolism to N-acetylprocainamide (NAPA), which has class 3 activity. Accumulation of NAPA is associated with torsade de pointes.

Answer 30

Lidocaine blocks activated and inactivated sodium channels with really rapid kinetics. Slows conduction velocity in depolarized cells, most selective for ischemic tissue. Shortens AP duration** -no change in QRS duration or QT. Therapeutic Use VENTRICLES: Arrhythmias associated with ACUTE myocardial infarction. Used for termination of ventricular tachycardia and prevention of ventricular fibrillation after acute ischemia. Used for digitalis-induced arrhythmias. Ineffective for ***supraventricular tachycardias, atrial fibrillation, and atrial flutter - no atrial stuff Class IB drugs shorten action potential duration and the refractory period. The inactivated state block ensures greater effects on cells with long action potentials. Increased inactivation and slow unbinding kinetics result in the selective depression of conduction in depolarized cells (state dependent block). Because these agents have little effect on normal cardiac cells, they have little effect on the ECG. 💧digitalis-induced arrhythmias. IB is Best post-MI. TOXICITY OF LIDOCAINE: CNS effects**(parethesia, slurred speech, and convulsions)***. tremor, nausea, lightheadedness, hearing disturbances, Pharmacokinetics: Extensive first-pass hepatic metabolism (only 3% of orally administered lidocaine appears in plasma). Given by I.V. Half-life is 1-2 hours. 🌞decrease AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Phenytoin can also fall into the IB category. Mexiletine: An orally active congener of lidocaine, mexiletine’s electrophysiologic and antiarrhythmic actions are similar to lidocaine and is used in the treatment of ventricular arrhythmias. Half life of 8-20 hrs. Used to treat chronic pain due to diabetic neuropathy and nerve injury.

Answer 31

flecainide, propafenone, moricizine. 1C drugs have slow unblocking kinetics --see decrease in upstroke of the action potential. Little effect on action potential duration, except in AV node and in bypass tracts. Therapeutic USE: supraventricular arrhythmias (AVNRT), terminating AFIB and maintaining normal rhythm + WPW arrhythmias 🎆Signiicantly prolongs ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration. USES: 🌈SVTs, including atrial ibrillation. Only as a last resort in refractory VT. TOXICITY🔥Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease. Toxicity: Provocation or exacerbation of potentially lethal arrhythmias, including the acceleration of ventricular rate in patients with atrial flutter, -Increased frequency of episodes of re-entrant ventricular tachycardia. In studies, flecainide and propafenone increased mortality in patients convalescing from MI. Can cause heart failure in patients with heart abnormalities.

Answer 32

Prototypes are propranolol and esmolol. Sotalol is a nonselective β-blocking drug that prolongs the action potential and is usually categorized as a class 3 drug USE: Beta-blockers control the ventricular rate in AFIB and AFLUTTER, suppress PVCs, and terminate and prevent recurrences of paroxysmal supraventricular tachycardias - TORSADES de pointes They reduce afterdepolarizations from catecholamine excess. These agents are contraindicated in patients with Wolff-Parkinson-White syndrome. The β-receptor-blocking action of propranolol and similar drugs lowers cAMP which results in the reduction of both sodium and calcium currents and the suppression of abnormal pacemakers. The AV node is particularly sensitive to β- blockers. Decreases phase 4 slope. Decreases myocardial oxygen demand. PROPRANOLOL: A non-selective antagonist, propranolol also exhibits Na+- channel blocking capabilities in vitro. Esmolol, a β1-selective agent, is an IV cardioselective beta-blocker (with an elimination half-life of about 9 minutes) that is effective in controlling the ventricular response in atrial flutter or fibrillation, particularly after cardiac surgery. Both therapeutic and adverse effects (hypotension, bradycardia) usually disappear within 30 minutes after stopping the infusion.

Answer 33

Ivabradine is a use-dependent drug that blocks “funny” current in the SA node and reduces heart rate without affecting myocardial contractility, ventricular repolarization or Intracardiac conduction. SHIFT trial (2010) evaluated patients with stable symptomatic heart failure with EF<35%, in sinus rhythm with a heart rate> 70 bpm who experienced a heart failure hospitalization within 1 year. Cardiovascular mortality or heart failure hospitation was reduced by 18% afer 22.9 months.

Answer 34

USE: Treatment of life-threatening ventricular arrhythmias, terminating AFIB/FLUTTER , and maintenance of sinus rhythm in patients with atrial fibrillation and VFIB (amiodarone) __________________________ Cardiac effects: Class III drugs prolong the action potential duration by blockade of potassium channels or by enhancing inward current. Action potential prolongation increases the effective refractory period and reduces the ability of the heart to respond to rapid tachycardias. Have little effect on phase 0 or conduction velocity. Action potential prolongation by many class III drugs (but not amiodarone) are reverse use-dependent, such that action potential prolongation is least dramatic at fast rates (where it is desirable) and most marked at slow rates, where it can contribute to the risk of torsade de pointes. ***Amiodarone is effective in most types of arrhythmias and is considered the most efficacious of all antiarrhythmic drugs. This is likely due to its capacity to block sodium, calcium, potassium channels, and β adrenoceptors. •  Elimination half-life is complex, with a rapid component of 3-10 days (50% of the drug) and a slower component of several weeks. **least likely to cause Torsades de Pointes because only one that is not reverse use dependance. Other drugs prolong AP most are slow rates which increases risk of TdP. Sotalol: A nonselective β-blocking drug that is more effective for many arrhythmias than other beta-blockers probably because of its potassium current activities. Ibutilide and Dofetilide: Adverse effects include QT interval prolongation and torsade-de-pointes. Use therapeutically for conversion of atrial flutter and fibrillation to normal sinus rhythm. [Adverse effects of CLASS III AA]: Dose-related incidence of excessive QT-interval prolongation, torsade-de-pointes as well as signs of excessive β-blockade such as sinus bradycardia or asthma. **dose related pulmonary toxicity (fibrosis), hepatic toxicity, thyroid hormone production, photodermatitis) Cardiac Effects: •  It is not reverse-use dependent. It prolongs the action potential duration over a wide range of heart rates and prolongs the the QT interval on the ECG by blockade of potassium channels •  Blocks inactivated sodium channels; its action potential prolonging action reinforces this effect. • Has weak adrenergic and calcium channel blocking actions, which slows of heart rate and atrioventricular node conduction. Amiodarone rarely causes new arrhythmias, perhaps because of its wide blocking effects. Extracardiac Toxicity (Many): Amiodarone causes pulmonary fibrosis, microcrystalline deposits in the cornea and skin, and thyroid dysfunction (inhibits conversion of T4 to T3). Interacts with warfarin and digoxin. Therapeutic Uses for Amiodarone: Amiodarone is more effective than most antiarrhythmic drugs for a wide spectrum of ventricular and supraventricular tachyarrhythmias: 1.   Atrial fibrillation 2.   Atrial tachycardia 3.   Ventricular tachycardia 4.   Ventricular flutter .

Answer 35

Prototype is verapamil. Another is Diltiazem. Nifedipine and other dihydropyridines are not useful as antiarrhythmics. Therapeutic USE: Major use is to prevent reentrant atrioventricular nodal **re-entrant tachycardia (AVNRT) PSVT. + AFIB - Only ATRIAL stuff unlike Lidocaine Contraindicated in Wolff-Parkinson-White syndrome. Cardiac Effects: Block both activated and inactivated L-type calcium channels decreasing the phase 4 slope. Conduction velocity is decreased and effective refractory period increased by these drugs. Extracardiac: Both verapamil and diltiazem also cause peripheral vasodilation. Toxicity: Atrioventricular block, sinus arrest in patients with sinus node disease, hypotension, constipation, lassitude, nervousness, and peripheral edema. Avoid use with β-blockers ( increase risk of heart failure).

Answer 36

ADENOSINE: Nucleoside that occurs naturally throughout the body. T 1/2 < 1 secs USE: • Drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90-95%) * *acute therapy for AFIB/AFLUTTER (, * **AVNRT - 1st line *  Activates inward rectifier K+ current, inhibits Ca2+ and If current, causing hyperpolarization and suppression of calcium-dependent action potentials. *   Inhibits AV nodal conduction and increases the AV nodal refractory period, but has lesser effects on the sinoatrial node.

Answer 37

Magnesium: Co-factor for Na/K ATPase. Antagonist of Ca2+ channels. Hypomagnesemia is known to contribute to several arrhythmias. Originally used for patients with digitalis-induced arrhythmias who have hypomagnesemia, intravenous infusion of Mg2+ has been shown effective for normomagnesemic patients with supraventricular arrhythmias and **Torsade de Pointe,

Answer 38

Digoxin: Used as an adjunctive agent, can help control ventricular response in atrial fibrillation or flutter and may terminate some paroxysmal (reentrant) supraventricular arrhythmias by *slowing AV conduction. -AVNRT AFIB AFLUTTER

Answer 39

Phosphodiesterase inhibitors; increases cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators for periphery (claudication). Think vasodilator + antiplatelet Uses: *Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin). Similar to milrenone, Adverse effects: Nausea, headache, facial lushing, hypotension, abdominal pain.

Answer 40

Inhibit NaCl reabsorption in early DCT > decreased diluting capacity of nephron. Decreased Ca2+ excretion. [2 CHANNELS] 1. apical NCC (cosymporter for absorption of sodium and chloride) 2. basolateral Sodium/calcium exchanger - reabsorbing calcium, excreting sodium - activity is enhanced when NCC is blocked -however only 10% of sodium is reabsorbed at this site so it is a weak diuretic Clinical use: 1. Hypertension 2. Heart failure 3. Nephrolithiasis due to idiopathic hypercalciuria 4. Nephrogenic diabetes insipidus (NDI) (vasopressin/ADH insensitivity) In NDI thiazides reduce plasma volume to lower GFR, which enhances proximal reabsorption of NaCl and water, causing decreased delivery of fluid to the diluting segments (collecting ducts). 5. -osteoporosis. Adverse effect: Hypokalemic metabolic alkalosis - enhanced proximal sodium reabsorption > increased proton/sodium exchange + increased potassium excretion Hyponatremia: It is due to a combination of hypovolemia-induced elevation of ADH, reduction in the diluting capacity of the kidney, and increased thirst. It can be prevented by reducing the dose of drug or limiting water intake. hyperGlycemia - cotransporter, increased proximal sodium reabsorption comes in with glucose hyperLipidemia, hyperUricemia, hyperCalcemia. Sulfa allergy. Potassium wasting: Diuretics that act upstream of the collecting tubule will increase Na+ delivery to this site and will enhance K+ secretion. This mechanism, combined with enhanced aldosterone secretion due to volume depletion, is the basis for most diuretic-induced K+ wasting and proton secretion.

Answer 41

Direct arteriolar vasodilator. -acts on potassium channels and hyperpolarize the cell. It prevents the opening of L type voltage dependent channels. ``` USES Androgenetic alopecia (pattern baldness), severe refractory hypertension. ```

Answer 42

B1 selective agent | Releases NO

Answer 43

[FA] Spironolactone and eplerenone are competitive aldosterone receptor antagonists in cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels (ENac) in the cortical collecting tubule. *Eplerenone is more selective and has less side-effects. Triamterene and amiloride block the ENaC Na+ channel in apical cells of the collecting tubule. Actions of triamterene and spironolactone are dependent on renal prostaglandin production. Thus, similar to loop diuretics and thiazides, the actions of triamterene and spironolactone may be inhibited by NSAIDS. ``` [CLINICAL USE:] **Hyperaldosteronism, K+ depletion, Heart Failure, hepatic ascites (spironolactone), nephrogenic DI (amiloride), antiandrogen. ``` Potassium sparing diuretic agents are most useful in states of mineralocorticoid excess, due either to primary hypersecretion (Conn’s syndrome, ectopic ACTH production) or to secondary aldosteronism (from heart failure, hepatic cirrhosis, nephrotic syndrome, and other conditions associated with diminished effective intravascular volume). Triamterene and Amiloride can be used to treat hypertension in Liddle’s syndrome, in which a gain-of-function mutation increases ENaC channel activity Thus, potassium-sparing diuretics of either type may be indicated in settings of enhanced mineralocorticoid secretion and continued delivery of Na+ to distal nephron sites where renal K+ wasting occurs. [ADVERSE EFFECTS] Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (eg, gynecomastia, antiandrogen effects). K+ sparing diuretics include blockers of the ENaC Na+ channel (triamterene, amiloride) and direct aldosterone antagonists (spironolactone, eplerenone) oppose aldosterone action in late distal tubule and collecting duct. •  Aldosterone release from the adrenal gland is promoted by: hyperkalemia, high angiotensin II (renin released by hypovolemia, hyponatremia, and beta1 agonists). •  Diuretics that increase Na+ delivery (loop diuretics, thiazides) to this site will therefore increase K+ and H+ secretion. •  Aldosterone antagonists prevent myocardial and vascular fibrosis. __________________________ •  Major side effects are 1. hyperkalemia, 2. hyperchloremic metabolic acidosis: By inhibiting H+ secretion in parallel with K+ secretion, the K-sparing diuretics can cause acidosis. (both get secreted together in the collecting tubule) 3. gynecomastia (spironolactone): Synthetic steroids may cause endocrine abnormalities by effects on other steroid receptors. Other effects (impotence, benign prostatic hyperplasia) have been reported with spironolactone. This can be avoided by using eplerenone, which is more specific.

Answer 44

non-dihydropyridines: Binds L-type calcium channels, preference for OPEN channels, with increased frequency of depolarizations (like heart), the drugs with decrease the amount of available open channels Equipotent for cardiac tissue and vasculature - - heart rate moderating (bradycardia) - reduced inotropism - heart failure - AV block - peripheral and coronary vasodilation Side effect: Constipation, SEVERE REFLEX TACHYCARDIA, hypotension, Non-dihydropyridine: cardiac depression, AV block, *hyperprolactinemia, constipation. Contraindicated in AV block or WPW + AFIB

Answer 45

Migraine headaches, tremors , performance anxiety

Answer 46

``` dihydropyridines (special features) AmLOOOOdipine - LOOOONNNG half life Clevidipine - IV ONLY Nimodipine - cerebral vessels (Nim is a brainy girl) ``` -preferentially target INACTIVATEd calcium channels - vascular smooth muscle cells have a higher RMP (-70) compared to cardiomyotes (-90). More calcium channels are inactive and will bind DHP at lower doses. -arterial vasodilators USES: Dihydropyridines (except nimodipine): hypertension, angina (including Prinzmetal), -Raynaud phenomenon. Nimodipine: subarachnoid hemorrhage (prevents cerebral vasospasm). Nicardipine, clevidipine: hypertensive urgency or emergency. ADVERSE EFFECTS: Dihydropyridine: peripheral edema, flushing, dizziness, *(gingival hyperplasia. Side Effect: SEVERE REFLEX TACHYCARDIA , hypotension, (effects of vasodilation: headaches, dizziness, light headedness, flushing, constipation),

Answer 47

Nitroglycerin side effect in industrial workers Over the weekend, the workers lose the tolerance and, when they are re-exposed on Monday, the drastic vasodilation produces a fast heart rate, dizziness, and a headache, this is referred to as "Monday Disease."

Answer 48

1. Hypertrophic cardiomyopathy (the smaller the ventricle the greater the obstruction) 2. mitral valve prolapse, the more full the heart, the better it will function, the click will occur later

Answer 49

Recombinant BNP which also acts to increase cGMP like NO. FOr decompensated heart failure counterregulation of the renin-angiotensin-aldosterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate.

Answer 50

Primary (essential) hypertension: Thiazide diuretics, ACE inhibitors, angiotensin II receptor blockers (ARBs), dihydropyridine Ca2+ channel blockers. Hypertension with heart failure Diuretics, ACE inhibitors/ARBs, β-blockers (compensated aka stable HF), aldosterone antagonists. *β-blockers must be used cautiously in decompensated HF and are contraindicated in cardiogenic shock. Hypertension with diabetes mellitus ACE inhibitors/ARBs, Ca2+ channel blockers, thiazide diuretics, β-blockers. *ACE inhibitors/ARBs are protective against diabetic nephropathy. Hypertension in pregnancy: Hydralazine, labetalol, methyldopa, nifedipine.

Answer 51

􀂃 Variant (Prinzmetal)—occurs at rest 2° to coronary artery spasm; transient ST elevation on ECG. Smoking is a risk factor, but hypertension and hypercholesterolemia are not. Triggers may include cocaine, alcohol, and triptans. Treat with Ca2+ channel blockers, nitrates, and smoking cessation (if applicable).

Answer 52

Inhibits the late phase of sodium current thereby reducing diastolic wall tension and oxygen consumption. Does not affect heart rate or contractility. CLINICAL USE Angina refractory to other medical therapies. ADVERSE EFFECTS Constipation, dizziness, headache, nausea, QT prolongation

Answer 53

USES; 1. Angina pectoris - decrease heart rate and contractility 2. MI - decrease mortality 3. Supraventricular tachycardia (decrease AV conduction velocity (class II antiarrhythmic) Metoprolol, esmolol, 4. Hypertension = decrease CO, decrease renin secretion due to B1 blockade 5. HF = decrease mortality (bisoprolol, carvediol, metoprolol) 6. Glaucoma = decrease production of aqueous humor - **Timolol 7. Variceal bleeding (decrease hepatic venous pressure gradient and portal hypertension - Nadolol, propranolol ADVERSE EffECTS: Erectile dysfunction, cardiovascular adverse effects (bradycardia, AV block, HF), CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), and asthma/COPD exacerbations *Use with caution in cocaine users due to risk of unopposed α-adrenergic receptor agonist activity SELECTIVITY: β1-selective antagonists (β1 > β2)—acebutolol (partial agonist), atenolol, betaxolol, bisoprolol, esmolol, metoprolol Selective antagonists mostly go from A to M (β1 with 1st half of alphabet) ``` Nonselective antagonists (β1 = β2)—nadolol, pindolol (partial agonist), propranolol, timolol Nonselective antagonists mostly go from N to Z (β2 with 2nd half of alphabet) ``` Nonselective α- and β-antagonists—carvedilol, labetalol Nonselective α- and β-antagonists have modified suffixes (instead of “-olol”) Nebivolol combines cardiac-selective β1-adrenergic blockade with stimulation of β3-receptors (activate nitric oxide synthase in the vasculature and decrease SVR)

Answer 54

Sildenafil (viagra) vardenafil, tadalafil. Inhibit PDE-5 > increase cGMP > prolonged smooth muscle relaxation in response to NO, HIGHER NO SENSITIVITY > increase blood flow in corpus cavernosum of penis, ---decrease pulmonary vascular resistance. Sildenafil, vardenafil, and tadalafil fill the penis. CLINICAL USE Erectile dysfunction, pulmonary hypertension, BPH (tadalafil only). ADVERSE EFFECTS Headache, flushing, dyspepsia, cyanopia (blue-tinted vision). ***Risk of life-threatening hypotension in patients taking nitrates. “Hot and sweaty,” but then Headache, Heartburn, Hypotension.

Answer 55

MECHANISM Direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I. CLINICAL USE: Hypertension. ADVERSE EFFECTS: Hyperkalemia, decreased GFR, hypotension, angioedema. Relatively contraindicated in patients already taking ACE inhibitors or ARBs.

Answer 56

ACT in PROXIMAL tubule and DESCENDING limb of Henle's loop where the cells are freely permeable to water. MECHANISM Osmotic diuretic. increase tubular fluid osmolarity > increase urine flow, decrease intracranial/intraocular pressure. **Osmotic diuretics INITIALLY expand the extracellular fluid volume, decrease blood viscosity, and inhibit renin release. These effects increase renal blood flow, thereby removing NaCl and urea from the renal medulla and decreasing medullary tonicity. Mannitol is not metabolized and is handled primarily by glomerular filtration without any important tubular reabsorption or secretion. Osmotic diuretics are poorly absorbed so they must be given parenterally. -Given orally mannitol causes osmotic diarrhea, which can be used to potentiate the effects of potassium-binding resins or eliminate toxic substances from the GI tract in conjunction with activated charcoal. CLINICAL USE A. To increase water excretion in preference to sodium excretion. B. Reduction of intracranial and intraocular pressure: C. To promote prompt removal of renal toxins (e.g., after use of radiocontrast agents), FA: drug overdose TOXICITY: A. Extracellular volume Expansion: Water expansion into extracellular compartment (before diuresis) causing hyponatremia. This effect can complicate congestive heart failure and may produce florid pulmonary edema. Headache, nausea, and vomiting are commonly observed in patients with osmotic diuretics. B. Dehydration and hypernatremia (after diuresis). From excessive use of osmotic diuretics without carefully monitoring serum ion composition and fluid balance. FA ADVERSE EFFECTS Pulmonary edema, dehydration. Contraindicated in anuria, HF.

Answer 57

MECHANISM in PROXIMAL tubule, inhibits the actions of NHE3, proton/sodium exchanger NORMAL MECHANISM: carbonic anhydrase converts carbonic acid into water and CO2. CO2 passively diffuses into the cell where a reverse carbonic anhydrase remakes carbonic acid, which this time splits into a proton and bicarbonate. The proton goes out into the lumen in exchange for sodium. Hence why you get a acidosis with acetazolamide. Hyperchloremic is because there is also a Cl-/bicarbonate exchanger, the more bicarb that gets out into the lumen, the more Cl- is reabsorbed Carbonic anhydrase inhibitor . blocks sodium bicarbonate reabsorption resulting in a decrease in sodium chloride reabsorption. Water Causes selflimited NaHCO3 diuresis and decreased total body HCO3 stores. *Effectiveness of acetazolamide decreases significantly over several days because of enhanced NaCl reabsorption at other sites due to bicarbonate depletion. CLINICAL USE A. Eye: glaucoma (decreases production of aqueous humor). Dorzolamide and brinzolamide are topically active C.A. inhibitors. B. Acute mountain sickness: Raise C02 content of tissues which in turn stabilizes deoxyhemoglobin. Useful for counteracting acute mountain sickness (during hyperventilation). Deoxyhemoglobin - gives off oxygen, so better oxygen delivery to tissues. C. To correct metabolic alkalosis that may develop in the setting of respiratory acidosis or due to excessive use of diuretics in patients with severe heart failure. D. Can be used to alkalinize the urine briefly (for solubilization of uric acid) or counteract metabolic alkalosis (from decreased total body K+, high levels of mineral corticoids, heart failure). E. Has anticonvulsant properties. Other Adverse effects are rare: paraesthesias, somnolence, allergic reactions in those sensitive to sulfonamides, Renal K+ wasting due to enhanced sodium reabsorption elsewehere. Contraindications: C.A. inhibitors should be avoided in patients with hepatic cirrhosis: Decreases NH4 + excretion may contribute to development of hepatic encephalopathy and coma.

Answer 58

ADH antagonists (conivaptan, tolvaptan) USES: SIADH (euvolemic hyponatremia.), block action of ADH at V2-receptor. ``` ADH increases the permeability of principal cells to water by binding to V2 receptors, thus increasing the number of water channel molecules (AQP2) on the apical surface in a cAMP dependent manner. ADH increases transport and synthesis of AQP2. ``` TOXICITY: A. Nephrogenic Diabetes Insipidus: • If serum Na+ is not monitored closely, ADH antagonists can cause severe hypernatremia and nephrogenic diabetes insipidus. B. Renal Failure: Both Li+ and demeclocycline have been reported to cause acute renal failure. Long term Li+ therapy may also cause chronic interstitial nephritis. C. Other: Adverse effects associated with Li+ therapy include tremulousness, mental obtundation, cardiotoxicity, thyroid dysfunction, and leukocytosis. Demeclocycline should be avoided in patients with liver disease.

Answer 59

1. Cardiogenic shock with maintained BP - dobutamine 2. Anaphylactic shock, cardiac arrest - epinephrine 3. Hypotension in sepsis and cardiognic shock -norepinephrine #2 drug for hypotension -phenylnephrine 5. Stokes Adams Attack - isoproternol 6. Pheochromocytoma: phenoxbenzamine or phentalomaine blocks catecholamine mediated vasoconstriction - irreversible receptor blockade 7. NE extravasation: phetolamine 8. Zosins - Tamulosin, terazosin, doxazosin

Answer 60

1. Warfarin 2. Statins 3. Ace inhibitors

Answer 61

Sildenafil (phosphodiesterase inhibitor, increasing levels of NO)

Answer 62

Lisinopril A common side effect of ACE inhibitors is cough along with angioneurotic edema which are also caused by high bradykinin.

Answer 63

1. Antithrombotic therapy 2. Beta blocker 3. Statin NOT oxygen therapy antiarrhythmic therapy -both increase mortality actually...

Answer 64

Furosemide Bumatenide Torsemide Ethacrynic acid -Ototoxicity

Answer 65

Triamterene - loop diuretic. Enoximone - phosphodiesterase inhibitors LCZ696- is a dual inhibitor of neprilysin and angiotensin receptors Tirofiban- binds to GPIIb/IIIa receptor

Answer 66

Enoxaparin - LMWH Ticagrelor - reversible binding to ADP Disopyramide - Class 1A drugs - can cause atropine like adverse effects Ivabradine - Class II antiarrhythmic that blocks funny current in the SA node, reducing heart rate without affect contractility. Dofetilide - class III antiarrhythmic Classically used therapeutically to convert aflutter and afib to normal sinus rhythm. Anti-ischemic drug for chronic angina. Blocks sodium, calcium, potassium currents. Lessens incidences of supraventricular arrhythmias including AF.

Answer 67

1. Pulmonary fibrosis 2. Crystalline deposits in the cornea and skin 3. Thyroid dysfunction

Answer 68

Methyldopa - a2 agonist - pregnancy hypertension. Nebivolol - long acting beta 1 selective with NO release Demeclocyline - ADH antagonist, can cause acute renal failure and also should be avoided in patients with liver disease. Cilostazol - intermittent claudication therapy, inhibition of phosphodiesterase 3 Colchicine - pericarditis

Answer 69

Gemfibrozil is a fibrate that stimulates lipoprotein lipase by activation of the PPARa protein. In so doing, it has beneficial effects on the serum lipid profile. Adverse effects of fibrates include elevation of liver enzymes and myositis.

Answer 70

The patient is experiencing pericarditis due to uremia secondary to chronic kidney disease in the setting of long-standing diabetes mellitus (DM). Pericarditis presents with pleuritic, positional chest pain that is often relieved by sitting forward and with a pericardial friction rub on physical examination. Diffuse ST segment elevations may be found on ECG, while an echocardiogram may be normal unless an effusion is also present. Pericarditis has multiple etiologies, including viral (coxsackie virus, echovirus, adenovirus, and HIV), bacterial (tuberculosis or Streptococcus pneumoniae or Staphylococcus aureus in the setting of endocarditis, pneumonia, or post-cardiac surgery), neoplastic, autoimmune, uremic, cardiovascular, or idiopathic. Treatment of pericarditis secondary to uremia is dialysis.

Answer 71

Because patients in cardiac tamponade are in a low-output state, they are preload dependent and require immediate volume resuscitation to maintain cardiac output. Positive inotropes such as dobutamine and pericardiocentesis would also be indicated in this patient after he has begun receiving IV hydration.

Answer 72

GLUCAGON! This patient is experiencing a propranolol overdose. Propranolol, a b-adrenergic receptor blocker, reduces heart rate and contractility due to antagonism of b1-receptors in the sinoatrial node. This lowers cardiac output. The goal of therapy should be restoring myocardial contractility and increasing cardiac output. Glucagon acts as a positive inotropic agent. It increases intracellular cAMP levels independently of adrenergic receptor signaling. Because its mechanism is unaffected by adrenergic blockade, glucagon is the drug of choice in b-blocker toxicity.

Answer 73

Potent P450 inhibitors 1. Azole antifungal drugs (ex Ketoconazole) 2. Erythromycin 3. Clarithromycin 4. Ciprofloxacin 5. Protease inhibitors (for HIV) (potent p450 inducers) 1. carbamazepine 2. phenytoin 3. phenobarbital 4. rifampin

Answer 74

Bivalirudin - indicated for unstable angina and directly inhibits thrombin.

Answer 75

Methylene blue - it will convert metHb back to hemoglobin by NADH-methemoglobin reductase. -Restoring blood O2 carrying capcity and tissue O2 availability. MetHb is Fe3_, lacks electron that binds oxygen. Can be due to nitric oxide ingestion

Answer 76

-chelating agent used to bind and clear heavy metals fro circulation such as lead.

Answer 77

used in cyanide ingestion

Answer 78

replenishes glutathione in patietns with acetaminophen overdose.

Answer 79

Bivalrudin - this is with or without HIT